Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.
Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.
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DOI：
10.1083/jcb.200912014
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发表时间：
2010-04-19
期刊：
影响因子：
--
通讯作者：
Parsons M
中科院分区：
文献类型：
--
作者：
Worth DC;Hodivala-Dilke K;Robinson SD;King SJ;Morton PE;Gertler FB;Humphries MJ;Parsons M
Loss of β3 integrin enhances turnover of focal adhesions and cell migration speed due to increased β1 integrin–talin interactions. Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of β3 integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3-null cells is preferentially associated with Rap1-GTP–interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP–RIAM complex at focal adhesions and subsequent increased binding of talin to β1 integrin. These data demonstrate a novel mechanism by which αvβ3 integrin acts to locally suppress β1 integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.
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影响因子：
7.3
作者：
Humphries JD;Byron A;Bass MD;Craig SE;Pinney JW;Knight D;Humphries MJ
通讯作者：
Humphries MJ
影响因子：
4.8
作者：
Barzik, M;Kotova, TI;Schafer, DA
通讯作者：
Schafer, DA
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
15.9
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
通讯作者：
Hynes, RO
影响因子：
3.3
作者：
Hashimoto, Yosuke;Parsons, Maddy;Adams, Josephine C.
通讯作者：
Adams, Josephine C.